The reason behind the High viral diversity is the mutation prone nature of the reverse transcriptase enzyme. In HIV, a high rate of spontaneous mutations has been ascribed to the absence of a 3”5′ exonuclease proofreading (Turner et al., 2003). Reverse transcriptase introduces a miss incorporation of a nucleotide once in each 10,000 base sets (Brenner et al., 2002). Along these lines, a patient will have every conceivable mix of HIV nucleotide changes soon after the infection of HIV. Understanding the intra-host and inter-host variability of the virus and genetic differences in patients is vital toward improvement of treatment results (Coffin, 1995).

4.6 RESISTANCE AND FITNESS
The principal inhibitors of viral replication were coordinated against reverse transcriptase and were nucleoside reverse transcriptase inhibitors (NRTIs). Nonetheless, antiretroviral drug treatment has additionally prompted the rise of drug resistance that possibly causes virological and clinical failure. Medication or drug resistance emerges suddenly as a consequence of the error prone reverse transcriptase and give rise to the accumulation of single or multiple mutations in the whole genome of the virus. Resistance mutations commonly happen in the gene targeted by a specific antiretroviral drug and cause the inhibitor’s efficacy to be reduced. Structural changes in the drug targets mediate the acquisition of resistance that decreases the affinity of the drug for the protein.
Michaud et al. said that ‘Genetic barrier for resistance refers to the number of nucleotide changes a virus needs to accumulate to become resistant against a given antiretroviral drug. A high genetic barrier indicates that the virus will need more genetic changes to become resistant, more efficient drug in terms of resistance. Due to high variability among viral populations, genetic barriers could be different for various antiretroviral dru